Deficits in receptor-mediated endocytosis and recycling in cells from mice with Gpr107 locus disruption

• Published in: Journal of cell science Vol. 127; no. Pt 18; pp. 3916 - 3927
• Main Authors: Zhou, Guo Ling, Na, Soon-Young, Niedra, Rasma, Seed, Brian
• Format: Journal Article
• Language: English
• Published: England 15.09.2014
• Subjects: Animals; Cell Membrane - genetics; Cell Membrane - metabolism; Endocytosis; Female; Low Density Lipoprotein Receptor-Related Protein-2 - genetics; Low Density Lipoprotein Receptor-Related Protein-2 - metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Protein Binding; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Receptors, G-Protein-Coupled - deficiency; Receptors, G-Protein-Coupled - genetics; Receptors, LDL - genetics; Receptors, LDL - metabolism; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; Vesicular Transport Proteins - genetics; Vesicular Transport Proteins - metabolism; Clathrin; Endocytosis; GPR107; Cubilin; Embryonic lethality
• ISSN: 0021-9533; 1477-9137
• DOI: 10.1242/jcs.135269

GPR107 is a type III integral membrane protein that was initially predicted to be a member of the family of G-protein-coupled receptors. This report shows that deletion of Gpr107 leads to an embryonic lethal phenotype that is characterized by a reduction in cubilin transcript abundance and a decrease in the representation of multiple genes implicated in the cubilin-megalin endocytic receptor complex (megalin is also known as LRP2). Gpr107-null fibroblast cells exhibit reduced transferrin internalization, decreased uptake of low-density lipoprotein (LDL) receptor-related protein-1 (LRP1) cargo and resistance to toxins. Colocalization studies and proteomic analyses suggest that GPR107 associates with clathrin and the retromer protein VPS35 and that GPR107 might be responsible for the return of receptors to the plasma membrane from endocytic compartments. The highly selective deficits observed in Gpr107-null cells indicate that GPR107 interacts directly or indirectly with a limited subset of surface receptors.